The frequency of the BLM p.Q548X (c.1642C>T) mutation in breast cancer patients from Russia is no higher than in the general population

Targeted next generation sequencing identifies functionally deleterious germline mutations in novel genes in early-onset/familial prostate cancer

“…On the other hand, RECQL4 belongs to a family of five RecQ helicases [ RECQL1 , WRN ( RECQL2 ), BLM ( RECQL3 ), RECQL4 and RECQL5 ] [ 55 ]. Interestingly, monoallelic mutations in RECQL1 and in the Bloom syndrome gene BLM have been described as risk factors for BrCa [ 56 , 57 ], although the BLM association has been contested by others [ 58 , 59 ]. According to the Uniprot database, the RECQL4 frameshift mutation c.2636del we here describe is not expected to affect the known functional domains of the protein, but more downstream (C-terminal) mutations in RECQL4 have been shown to cause RTS or GBS [ 55 ] and the C-terminal seems to be necessary for RECQL4 nucleolar localization through interaction with PARP-1 [ 60 ], therefore making very likely its deleterious nature.…”

The frequency of the BLM*p.Q548X (c.1642C > T) mutation in breast cancer patients from Russia

“…To the Editor We appreciate the work of Anisimenko and colleagues [1] who attempted to replicate our reports on the association of the BLM*p.Q548X mutation with breast cancer risk in Eastern European populations, including Russians [2,3]. Their case-control study from Novosibirsk failed to find an increased frequency of this rare Slavic founder mutation in breast cancer patients, and the authors suggest that some recruitment bias could have led to differences between the studies.…”

“…The case-control study of Anisimenko et al is well powered for the detection of over three-fold risks, yet there is an overlap of risk estimates at OR 1.5-2.3 in all studies so far [3], and this is well in the range of effect sizes for truncating mutations in accepted breast cancer susceptibility genes such as CHEK2 [4] or ATM [5]. If we add the results reported by Anisimenko et al [1] to our meta-analysis of published casecontrol studies for the BLM*p.Q548X mutation, the overall association with breast cancer still persists (Fig. 1), with little evidence for heterogeneity between studies (p = 0.15), and the combined odds ratio would be consistent with an intermediate-penetrance susceptibility allele for breast cancer (Mantel-Haenszel OR 2.3; 95 % CI 1.3, 4.0; p = 0.003, fixed-effects model).…”

First Two Cases of Bloom Syndrome in Russia: Lack of Skin Manifestations in a BLM c.1642C>T (p.Q548X) Homozygote as a Likely Cause of Underdiagnosis

“…We recently analyzed the BLM gene as a candidate for hereditary breast cancer (BC), and revealed its association with BC risk [Sokolenko et al, 2012]. The BC-predisposing role of BLM was later confirmed by exome sequencing and case-control studies [Thompson et al, 2012;Prokofyeva et al, 2013], although a negative report has been published as well [Anisimenko et al, 2014]. Interestingly, these studies identified a founder BLM mutation c.1642C>T (p.Q548X), with the frequency of its heterozygous carriers in Slavic populations usually falling within the range of 0.2-0.6% ( Table 1 ).…”